J . Chem. Tech. Biotechnol. 1990, 49, 243-247

Synthesis and Biological Activity of Some 5-Substituted Aminomethyl-8-hydroxyquinoline-7-sulp honic Acids A. S. Yanni" & A. M. Mohharamb "Chemistry Department, bBotany Department, Faculty of Science, Assiut University, Assiut, Egypt (Received 20 November 1989; accepted 24 January 1990) ABSTRACT 5-Aryl (or alkyl)-8-hydroxyquinoline-7-sulphonic acids have been prepared by the Mannich reaction of 8-hydroxyquinoline-7-sulphonic acid with primary and secondary amines. Their bactericidal activities have been determined. Key words: Mannich derivatives, 8-quinolinol-7-sulphonic acids.

1 INTRODUCTION Substituted 8-hydroxyquinolines are reported as potential am~ebicides;'-~ the are Mannich derivatives of 5-benzyl and 5-(pchlorobenzoyl)-8-hydroxyquinolines also reported as potential am~ebicides.~ In continuation of the authors previous work of Mannich derivatives of 8-hydroxyquinoline-5-sulphonicacids,' the Mannich derivatives of 8-hydroxyquinoline-7-sulphonicacid were prepared in order to evaluate their biological activities in comparison with the previous work.' The title compounds were prepared through Mannich reaction on 8hydroxyquinoline-7-sulphonic acid according to the usual and identified by elemental analysis and spectral data (Table 1). The UV spectra in methanol displayed a-n* transition bands due to phenyl and heterocyclic rings around (245(s),260 (shoulder),310-330,and 360-390 nm (broad). IR spectra showed absorptions at 3450 (vOH), 3100-3280 (vNH), 2850-2920 (vCH2),and 1580-1640 cm-' ( v ~ = ~The ) . NMR (DMSO) of compound 2 revealed signals at 6 2.5 (s, 2H, CH,), 6 3.33 (s, 10H,N D ) , and 6 7.3-8.7 (m, 5H,hydroxyquinoline). The bactericidal activities of selected compounds were determined by usual disc assay method against Staphylococcus aureus, Bacillus cereus, B. subtilis, 243 J . Chem. Tech. Biotechnol. 0268-2575/90/$03.500 1990 Society of Chemical Industry. Printed in Great

Britain

A. S . Yanni, A . M . Mohharam

244

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c?$

OH

Ig, R =-c6H4-cOOH-p

la, R = - c 6 H 5 lb, R =-C6H4-cH3-p k,R =-c6H4-oCH3-p Id, R = -CbH,-OH-p le, R = -C,H,-NO,-p If, R=-c6H,-cI-p

2

OJ

Ih, R=-l-Cl0H, li, R =-3-C,H,N Ij, R = -CH, Ik, R = -C4H9 11, R =-CH2C02H

3

4

Micrococcus luteus, Proteus vulgaris, Pseudomonas aeruginosa, Escherichia coli, and Serratia sp. Most of them showed remarkable bactericidal activity against B. cereus, B. subtilis, M . luteus and E . coli. Some of them exhibited moderate activity against Proteus vulgaris, S. aureus, Serratia sp. and Pseudomonas auruginosa (Table 2). It was noticed that phenylaminomethyl derivative la and naphthylaminomethyl lg have the least activity. Substituted phenylaminomethyl derivatives were more effective as bactericides than alkylaminomethyl derivatives; from previous studies it is also noteworthy that generally the isomeric 7-substituted aminomethyl-8hydroxyquinoline-5-sulphonic acids are less potent than 5-substituted aminomethyl-8-hydroxyquinoline-7-sulphonic except for the methylaminomethyl derivative.

2 EXPERIMENTAL

Melting points are uncorrected. IR spectra (KBr) were recorded on a Unicam S P 200 G spectrophotometer using 1 cm matched silica cells, UV-visible absorption spectra were recorded on a Pye Unicam S P 800 ultraviolet recording spectrophotometer using 1 cm matched silica cells: NMR spectra (DMSO) were measured on a Varian 90 MHz spectrometer.

2.1 5-Aryl (or alk yl) aminomethyl-8-hydroxyquinoline-7-sulphonicacids laA mixture of 8-hydroxyquinoline-7-sulphonic acid (0.004 mol), paraformaldehyde

(0.004 mol) and the primary aromatic or aliphatic amine (0.004 mol) was refluxed in ethanol (50 ml) for 30-50 h. The separated products (la-) were filtered and

_

‘SPZ ‘SPZ ‘OSZ ‘SPZ ‘9PZ ‘ZPZ

- _

8LE ‘OEE ‘Z9Z 8LE ‘Off ‘09Z 06E ‘SZE ‘(YS)S9Z SLE ‘OIE ‘(9S)SSZ 08E ‘OZE ‘E9Z 8LE ‘81E ‘09Z

_ 06E ‘Off ‘EOE ‘09Z ‘ZPZ 08C ‘OIE ‘WZ ‘ZPZ S8E ‘EOE ‘(V)Z9Z ‘8PZ S8E ‘(9s)OIE ‘09Z ‘ZPZ E9E ‘SOE ‘Z9Z ‘ZPZ 08E ‘SO€ ‘(qS)Z9Z ‘9PZ 08C ‘SOE ‘(W)Z9Z ‘8PZ SLE ‘SOE ‘(YS)09Z ‘9PZ

(ZE.01) 10.01 (EI.01) 88.6 (85.6) P66 (91.01) E6.6 (Zf.01) 80.01 (P6.11) Z9.11 (L9.6) S.Z6 (ZP.8) 02.8 (9S.8) 02.8 (EL-6) SP.6 (ES.8) 52.8 (SZ-6) S8-8 (88.8) 09.8 (OE-6) S6-8 (OL.6) SE.6

(IEO-6) 28.8 (98.8) P9.8 (66.8) 69.8 (ZE.6) 01.8 (EO-6) 58.8 (SP.01) 11.01 (69.ZI) SZ.ZI (LC-L) 0I.L (6P.L) 0Z.L (15.8) 52.8 (OZ.11) 06.01 (60.8) SL.L (8L.L) 0P.L (91.8) 08.L (89.8) 01.8

S’OzN8’H’’3 SSOZN9’H’’3 S’OzN8’HS’3 S9OZNZ’HZ’3 S’OzN8’H*’3 S”O‘NZ’H’’3 S’OENC’HS’3 S’OzN9’HoZ3 S90ZN”HL’3 *OSzNE’H9’3 S90ENE’H9’3 SSO‘N”H9’3 SsOZN9’H‘’3 S’OzN9’HL’3 S’OZN’’H9’3

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BI

41

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a1

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UMOJa

UMOla

I1

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91

Ofz 08Z SPZ S LZ

umo1a

alEd

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MO(@

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I)

p.i. = Partial inhibition. Clear zone.

b ~ .= ~ .

a

11

lk

li

lh

1g

la lb lc le If

Compound

7

-

13 (c.z.) 13 (c.z.) 13 (c.z.)

-

-

18 (c.z.)

-

15 (c.z.)

14 (c.z.)

-

6 (pi)

10

7 (pi.)

-

-

15 (c.z.) -

-

Staphylococcus aureus

-

7 (pi) -

-

Proteus vulgaris

8 (p.i.)

-

Serratia Pseudomonas sp. aeruginosa

13 ( p i ) 25 (C.Z.)

-

-

8 (c.z.) 6 (p.i.)

-

(C.Z.)

6 (pi.)

8

10 (p.i.)

-

8 (C.Z.)* 8 (c.z.)

10 (C.Z.)

15 (c.i.) 10 (C.Z.) 6 (c.z.) 8 (c.z.) 12 (C.Z.)

-

10 (C.Z.) 12 (p.i.)

Bacillus subtilis

Bacillus cereus

Organism

25

(C.Z.)

-

-

10 (p.i.) 8 (p.i.) 10 (p.i.) 10 (p.i.) 6 (pi.)

-

19 (pi)" 15 (pi.) 12 (p.i.) 15 (c.z.) 10 (C.Z.) 10 (C.Z.) 10 (C.Z.) 10 (C.Z.) 12 (C.Z.) 14 (c.z.)

Micrococcus Escherichia luteus coli

TABLE 2 Effect of Selected Compounds of 1 on Some Gram Positive and Some Gram Negative Bacterial Species Using Disc Plate Method (Disc Diameter 5 mm)

F

P

3

-_

3

v,

P

Aminomethyl-8-hydroxyquinoline-7-sulphonicacids

247

crystallised from glacial acetic acid, yield 6&70 %. These compounds were insoluble in chloroform, carbon tetrachloride, dioxane, ether and acetone, moderately soluble in glacial acetic acid, sparingly soluble in ethanol and methanol, and soluble in dilute HCl. Their characterisation data are given in Table 1. 5-Piperidino (and morphilino) methyl-8-hydroxyquinoline-7-sulphonicacids (2 and 3 respectively) and 5-diethylaminomethyl-7-sulphonicacid (4) were also prepared following the above procedure; their physical data are also given in Table 1.

2.2 Antibacterial activity of compounds 1 The antibacterial activity of compounds l a x , e-h and j-l was determined by the usual disc assay method against S. aureus, B. cereus, B. subtilis, M . luteus, E . coli, Proteus vulgaris, Pseudomonas aeruginosa and Serratia sp. at a concentration of 5 pg per disc (Table 2). The culture medium used was of normal nutrient agar containing 1 g yeast dmP3.The bacterial suspension was prepared by adding 1 cm3 of sterile distilled water to a 24-hour-old culture of the test organism grown on nutrient agar slant.

REFERENCES Gopalchari, R.,Popli, S. P., Nitya, N. & Dahr, M.L., J. Scient. Ind. Res., 13B (1954) 15. Gopalchari, R. & Dahr, M. L., J. Scient. Ind. Res., 19C (1960) 233. Gopalchari, R.,J. Scient. Ind. Res., 16C (1957) 143; 19C (1960) 296; 21B (1961) 266. Porter, Th. H., Sketton, F. S. & Folkers, K., J . Med. Chem., 15 (1972) 34. 5. Yanni, A. S. & Timawy, A. A., Indian J . Chem., 21B (1982) 705.

1. 2. 3. 4.